The value of administering active principles in the form of sustained release compositions has been known for a long time, whether they be conventional pharmaceutical products, for example steroids, peptides or proteins (cf., for example, U.S. Pat. No. 3,773,919 to Boswell), or products for use in plant protection. The formulations adopted can take the form of microparticles in which the active principle is incorporated in a biodegradable polymer or copolymer such as a polylactide/coglycolide copolymer (PLGA).
It has been found that, especially when a relatively constant or, in any case, uninterrupted release mode is sought--this mode being referred to for example as "monophase" in European Patent EP 58 481--PLGA-type polymers of relatively low molecular weight, i.e. of low viscosity, are required. European patents EP 21 234 (cf. Example 8.B.2. describing a copolymer of intrinsic viscosity 0.5 dl/g), EP 52 510, in which a copolymer with a viscosity of 0.38 dl/g in hexafluoroisopropanol (HFIP) is tested in vivo, and EP 26 599, which describes, by way of example, polymers with viscosities of 0.12 to 0.20 dl/g and claims polymers with a viscosity of 0.08 to 0.30 dl/g, may be mentioned in this connection. The polymers described in said patents are presented as producing constant release compositions. The compositions of Patent EP 26 599 can contain fertility control agents, for example.
It is moreover important to note in this respect that in the opposition proceedings relating to European Patent EP 58 481, which are still in progress on the date of filing of the present patent application, the Applicant limited its main claim to polymers of low viscosity (below 0.3 or 0.5 dl/g), which, according to the Applicant, are the only ones capable of permitting a release of the monophase type.
Furthermore, when a longer release period, for example of more than one month, is sought, more complex problems appear and a solution proposed by Patent EP 0 302 582, for example, consists in mixing several types of microcapsules made up of polymers of different viscosities.